Expression of Different Glycoforms of Membrane Mucin(MUC1) and Secretory Mucin (MUC2, MUC5AC and MUC6) in Pancreatic Neoplasms

Abstract

Our previous studies of pancreatic tumors have demonstrated that invasive ductal carcinoma (IDC) usually showed expression of MUC1 (membrane bound type mucin) detected by monoclonal antibody DF3, whereas intraductal papillary-mucinous neoplasm (IPMN) showed no expression of MUC1. In the present study, we examined 50 IDCs, and 63 IPMNs which were morphologically classified into two histological subtypes, "dark cell type" (IPMN-D, 27 cases) and "clear cell type" (IPMN-C, 36 cases). Patients with either type of IPMN showed significantly better survival than those with IDC. To clarify the relationship of the expression patterns of mucins with their biological behavior, we examined the expression profiles of various glycoforms of membrane mucin (MUC1) and secretory mucin (MUC2, MUC5AC and MUC6) in the neoplasms using immunohistochemistry. IDCs showed high expression of all the glycoforms of MUC1 (66%-98%). In contrast, IPMNs-D showed no or low expression of all the glycoforms of MUC1 (0%-4%), while IPMNs-C showed low expression of poorly glycosylated MUC1 (3%-6%), but expression of sialylated MUC1 (41%) and fully glycosylated MUC1 (69%). Expression of MUC2 was negative (0%) in IDC, high (96%) in IPMN-D and low (3%) in IPMN-C. MUC5AC was highly expressed in all types. MUC6 expression was higher in IPMNs-C (92%) than in IDCs (56%) and IPMNs-D (37%). In conclusion, the present study demonstrated that IDCs showed high expression of all the glycoforms of MUC1, and also that two types of IPMNs showed different expression patterns of glycosylated MUC1 as well as MUC2 and MUC6. These different expression patterns of mucins may be related with the malignancy potential of pancreatic neoplasms.

Expression of Mucins in the Human Fetal and Neonatal Stomach

“…Higashi et al [14] reported that neuramidase treatment makes possible detection of MUC1 core in biliary adenocarcinoma cells expressing sialylated and glycosylated MUC1. Horinouchi et al [17] reported various expression patterns of MUC1 core, sialylated MUC1 and fully glycosylated MUC1 in pancreatic neoplastic cells. Therefore, expression of MUC1 in the neoplastic cells is modified by the activity of the related enzymes under neoplastic changes.…”

“…They were Ma552 (MUC1 core) against hexapeptide sequence (DTRPAP) in the tandem repeat region of human MUC1 core glycoprotein [32]; Ma695 (so-called sialylated MUC1 [17]) against the sialic acid-dependent carbohydrate epitope of the human MUC1 glycoprotein [32]; Ccp58 (MUC2) against human MUC2 glycoprotein; CLH2 (MUC5AC) against human MUC5AC glycoprotein; and CLH5 (MUC6) against human MUC6 glycoprotein.…”

Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: Prognostic impact

“…Mucins are present at the surface of most epithelial cells and play a role in protection and lubrication. It has been suggested that expression of mucins is associated with clinicopathological findings and patient survival in tumors that arise in various organs (5)(6)(7)(8). MUC1 overexpression is most evident, and these rigid mucin glycoproteins located on cancer cells play a role in metastasis by inhibiting tumor cell adhesion and allowing escape from immune surveillance (9)(10)(11).…”

Expression Profiles of MUC Mucin Core Protein in the Intrahepatic Biliary System: Physiological Distribution and Pathological Significance

“…There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B and MUC6) and transmembrane mucins (MUC1, MUC3, MUC4, MUC12 and MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15 and MUC16) ( Table 1). Each MUC mucin shows a characteristic distribution in organs and cell types [4,6,7] (Table 1). In these MUC mucins, MUC1 mucin is widely distributed in epithelial cells, and the epitope of epithelial membrane antigen (EMA), a common immunohistochemical marker to detect epithelial cells and carcinomas, is on the glycosylated form of the MUC1 mucin.…”

“…In these MUC mucins, MUC1 mucin is widely distributed in epithelial cells, and the epitope of epithelial membrane antigen (EMA), a common immunohistochemical marker to detect epithelial cells and carcinomas, is on the glycosylated form of the MUC1 mucin. Altered mucin gene expression has been reported in inflammatory diseases and carcinomas of the GI tract and breast [4,6,7]. Accumulating data suggest that each MUC mucin has different properties, for example, the presence of an EGF-like domain, a transmembrane region and a gel-forming capacity, and may have diverse functions.…”